{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T18:35:58Z","timestamp":1778524558802,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011105","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000}}],"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20200088"],"award-info":[{"award-number":["BK20200088"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802030"],"award-info":[{"award-number":["81802030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"grant from Key Laboratory of Pathogen Biology of Jiangsu Province","award":["KLPBJP-K202008"],"award-info":[{"award-number":["KLPBJP-K202008"]}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20211586"],"award-info":[{"award-number":["BK20211586"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> is the most successful parasite worldwide. It is of great interest to understand how <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> induce different immune responses in different hosts. In this study, we found that a peptide of <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> microneme protein MIC3 induced TNF-\u03b1 production, NF-\u03baB phosphorylation, <jats:italic>iNOS<\/jats:italic> transcription and Ly6C expression in mouse macrophage RAW264.7 cells. MyD88 inhibition, small interfering RNA against <jats:italic>Tlr11<\/jats:italic> and CRISPR\/Cas9-mediated knock-out of <jats:italic>Tlr11<\/jats:italic> all reduced MIC3-induced TNF-\u03b1 production, NF-\u03baB phosphorylation, <jats:italic>iNOS<\/jats:italic> transcription and Ly6C expression. Additionally, we determined the location of MIC3 peptide in mouse macrophages using immunofluorescence. MIC3 could both adhere to the cell membrane of mouse macrophages and enter the cells. These results suggest that MIC3 triggered the immune responses in mouse macrophages via TLR11\/MyD88\/NF-\u03baB pathway. It is known that human macrophages lacking TLR11. We predicted that the immune responses induced by MIC3 in human macrophages were significantly different from those in mouse macrophages. As expected, MIC3 peptide failed to induce TNF-\u03b1 expression, <jats:italic>iNOS<\/jats:italic> expression and NF-\u03baB phosphorylation in human THP-1 derived macrophages. MIC3 induced macrophage immune responses via TLR11. Intriguingly, the amino acid sequence of MIC3 is completely different from the well-known TLR11 ligand profilin, which generates a potent IL-12p40, TNF-\u03b1 and IL-6 response. In marked contrast to profilin, MIC3 could not induce IL-12p40 expression in both mouse RAW264.7 cells and human THP-1 derived macrophages. Furthermore, the simulated tertiary structure of MIC3 peptide shows poor similarity with the crystal structure of profilin, suggesting that MIC3 might be a different ligand from profilin. These findings about MIC3 and TLR11 will provide us with important insights into the pathogenesis of toxoplasmosis and coevolution during host-parasite interaction.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011105","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T19:39:52Z","timestamp":1675366792000},"page":"e0011105","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Toxoplasma gondii microneme protein MIC3 induces macrophage TNF-\u03b1 production and Ly6C expression via TLR11\/MyD88 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